SD-Rosa-hAGT/H11-hREN Rat

The AGT gene encodes the precursor of angiotensinogen, primarily expressed in the liver. It serves as a rate-limiting substrate in the renin-angiotensin system (RAS). When blood pressure decreases, the angiotensinogen precursor is cleaved by renin to generate angiotensin I (Ang I) in response. Subsequently, Ang I is further processed by angiotensin-converting enzyme (ACE) to produce the physiologically active enzyme angiotensin II (Ang II), which regulates blood pressure ^[1]. This protein is involved in maintaining blood pressure, body fluid, and electrolyte homeostasis, and plays a role in the pathogenesis of primary hypertension and preeclampsia ^[2-3]. Mutations in the AGT gene are closely associated with susceptibility to primary hypertension and can lead to renal tubular dysplasia ^[4]. Additionally, defects in this gene are associated with non-familial structural atrial fibrillation and inflammatory bowel disease ^[5].

The REN gene encodes renin, another integral component of the RAS, which is fundamental for regulating blood pressure and electrolyte balance ^[6]. Primarily expressed in the juxtaglomerular cells of the kidneys, renin is secreted into the bloodstream where it functions to cleave angiotensinogen, produced by the liver, into angiotensin I ^[7]. This initiates a cascade leading to the formation of angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release from the adrenal glands, ultimately increasing blood pressure and sodium retention ^[8]. Mutations in the REN gene have been linked to several renal disorders, including familial juvenile hyperuricemic nephropathy type II, familial hyperreninemia, and renal tubular dysgenesis ^[9].

The SD-Rosa-hAGT/H11-hREN rats are a humanized model obtained by mating SD-Rosa-hAGT rats with SD-H11-hREN rats. This model can be used for research on the regulation of blood pressure, body fluid and electrolyte homeostasis, and the pathological mechanisms and treatment methods of primary hypertension, preeclampsia, renal tubular hypoplasia, non-familial structural atrial fibrillation, inflammatory bowel disease, etc. Moreover, it can be applied to the development of antihypertensive drugs targeting the renin-angiotensin system (RAS).